Ion-channel concept

Dmg receptors are chemical entities which are typically, but not exclusively, small molecules that interact with cellular components, frequently at the plasma membrane level (1,2). There are many types of receptors heat, light, immune, hormone, ion channel, toxin, and vims are but a few that can excite a cell. The receptor concept can be appHed generally to signal recognition processes where a chemical or physical signal is recognized. This recognition is translated into response (Fig. 3) and the process can be seen as a flow of information. 

Our knowledge of biological membrane ultrastructure has increased considerably over the years as a result of rapid advances in instrumentation. Although there is still controversy over the most correct biological membrane model, the concept of membrane structure presented by Davson and Danielli of a lipid bilayer is perhaps the one best accepted [12,13]. The most current version of that basic model, illustrated in Fig. 7, is referred to as the fluid mosaic model of membrane structure. This model is consistent with what we have learned about the existence of specific ion channels and receptors within and along surface membranes. 

Studies on artificial ion channels are expected to provide important information on molecular mechanisms and to deepen our understanding of natural ion channels through the establishment of a detailed structure-function relationship. At the same time, the research will contribute to the fascinating area of nanoscale transducers, and may eventually lead to the development of so-called molecular ionics. Here, the author would like to describe the basic concept for the molecular design of various artificial ion channels and to compare their characteristics in the hope of stimulating a future explosion of this research field. Special attention is focused on non-peptidic approaches. Helical bundle approaches " and studies on modified antibiotics " are beyond the scope of this review. 

Both the inhaled and the intravenous anesthetics can depress spontaneous and evoked activity of neurons in many regions of the brain. Older concepts of the mechanism of anesthesia evoked nonspecific interactions of these agents with the lipid matrix of the nerve membrane (the so-called Meyer-Overton principle)—interactions that were thought to lead to secondary changes in ion flux. More recently, evidence has accumulated suggesting that the modification of ion currents by anesthetics results from more direct interactions with specific nerve membrane components. The ionic mechanisms involved for different anesthetics may vary, but at clinically relevant concentrations they appear to involve interactions with members of the ligand-gated ion channel family. 

Fig. 22. DeGrado s concept for the development of artificial ion channels. The self-assemblage in a bilayer membrane of an amphiphilic peptide unit generates a hydrophobic oi-helix bundle structure with a polar channel in the middle...

Friederich P. Basic concepts of ion channel physiology and anaesthetic drug effects. Eur J Anaesthesiol. 2003 20 343-353. 

In a reversed type of approach, we used the pseudoreceptor modeling concept not to develop a tool for SAR predictions but to characterize two discrete ion channel modes on a molecular level [28]. For this purpose, a set of 13 well-characterized 1,4-dihydropyridine (DHP) derivatives with experimentally determined dissociation constants (Kf) for the voltage-gated calcium channel (VGCC) in the resting state (rs) and the open/inactivated state (is) were investigated (Table 5.2). 

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